Microfluidic system having monolithic nanoplasmonic structures

Abstract

A microfluidic system has a monolithic biocompatible substrate with both a surface having an ordered array of nano-scale elements for plasmonic response monitoring and a network of microchannels. Advantageously, low-volume consumption, rapid low-cost fabrication of molds with easily interchangeable microfluidic channel layouts, mass production, and in situ label-free real-time detection of cellular response, viability, behavior and biomolecular binding using plasmonic techniques can be provided. A ratio of greater than 0.2 of the cross-sectional dimension and the spacing between the nano-scale elements is useful for plasmonic response monitoring. Producing such a system involves a master mold with the nano-scale elements etched into a hard substrate, and the network provided in a soft membrane bonded to the hard substrate. A stamp may be created by setting a settable liquid polymer or metal placed in the master mold. Features of the intended device can be transferred to a polymeric substrate using the stamp.

The invention claimed is: 
     
       1. A microfluidic device comprising a monolithic polymeric substrate patterned with one or more micro-scale channels in fluid communication with one or more microfluidic chambers, a surface in the monolithic polymeric substrate comprising an ordered array of nano-scale elements suitable for plasmonic resonance reading of a fluid on the surface, the nano-scale elements having cross-sectional dimensions in a range of from 10 nm to 1000 nm, the array having a spacing distance between the elements where a cross-sectional dimension to spacing distance ratio is greater than 0.2. 
     
     
       2. The device according to  claim 1 , wherein the polymeric substrate comprises a thermoplastic polymer, a biodegradable polymer, an elastomer, polydimethylsiloxane or any blend thereof. 
     
     
       3. The device according to  claim 1 , wherein the device is a cell culture system and comprises one or more valves, conduits, inlets or outlets, wherein at least one of the ordered arrays of nano-scale elements is in at least one of the microfluidic chambers, and the nanoscale elements are patterned on microstructures to provide two levels of topographical cues. 
     
     
       4. The device according to  claim 1 , wherein the nano-scale elements comprise one or more of nanopillars, nanoposts, nanodots, nanorods, nanopyramids, nanocrescents, nanodisks, nanodomes, nanoholes, nanogratings and nanogrooves with the aspect ratio of individual nanoscale elements being in a range of from 10:1 to 1:10 and the nano-scale elements are metalized with their cross-sectional dimension to spacing distance ratio is in a range of from 0.2 to 1.5. 
     
     
       5. The device according to  claim 1 , wherein size, spacing, geometry or any combination thereof of the nano-scale elements in the ordered array have standard deviations from their respective averages of no more than 3%. 
     
     
       6. The device according to  claim 1 , wherein the cross-sectional dimension to spacing distance ratio is in a range of from 0.2 to 1.5. 
     
     
       7. The device according to  claim 1 , wherein the nano-scale elements are metalized. 
     
     
       8. The device according to  claim 1 , wherein:
 the nano-scale elements are patterned on microstructures to provide two levels of topographical cues; and 
 an aspect ratio of individual nano-scale elements is in a range of from 10:1 to 1:10. 
 
     
     
       9. The device according to  claim 1 , wherein at least one ordered array of nano-scale elements is in a microfluidic chamber. 
     
     
       10. The device according the  claim 1 , wherein the monolithic polymeric substrate comprises a cycloolefin polymer, or a thermoplastic elastomer. 
     
     
       11. The device according the  claim 1 , wherein the device is a cell culture system. 
     
     
       12. The device according the  claim 1 , wherein at least part of the ordered array of nano-scale elements is in at least one of the microfluidic chambers. 
     
     
       13. The device according to  claim 1 , wherein the cross-sectional dimensions to spacing distance ratio is in a range of from 0.5 to 1. 
     
     
       14. The device according to  claim 1 , wherein the nano-scale elements comprise one of more of nanopillars, nanoposts, nanodots, nanorods, nanopyramids, nanocrescents, nanodisks, nanodomes, nanoholes, nanogratings, and nanogrooves. 
     
     
       15. The device according to  claim 1 , further comprising: one or move valves, conduits, inlets, or outlets. 
     
     
       16. The device according to  claim 1 , wherein the nano-scale elements are patterned on microstructures to provide two levels of topographical cues. 
     
     
       17. The device according the  claim 1 , wherein an aspect ratio of individual nano-scale elements is in a range of from 10:1 to 1:10. 
     
     
       18. A method for using the device defined in  claim 1 , the method comprising: loading the one of more microfluidic chambers with cells; allowing cell attachment to the one or more microfluidic chambers; and taking plasmonic resonance readings of cells. 
     
     
       19. The method according to  claim 18 , wherein one of the plasmonic resonance readings is made according to reflection-mode surface plasmon resonance, transmission-mode surface plasmon resonance, localized surface plasmon resonance or surface-enhanced Raman spectroscopy. 
     
     
       20. The method according to  claim 18 , wherein the plasmonic resonance monitors cellular behavior, motility, attachment, viability, biomolecule interactions or any combination thereof. 
     
     
       21. The method according to  claim 18 , wherein the method is for screening molecular or cellular targets, cellular identification, screening single cells for RNA or protein expression, monitoring cell response to different stimuli, genetic diagnostic screening at single cell level, or performing single cell signal transduction studies. 
     
     
       22. The method according the  claim 18 , wherein loading the cells comprises using pressure-driven flow to transport cells in suspension from a plurality of cell-loading channels to a plurality of the one or more microfluidic chambers, which are cell culture chambers. 
     
     
       23. The method according to  claim 22 , further comprising: injecting fresh media in each of the cell culture chambers via a plurality of perfusion channels, following cell attachment. 
     
     
       24. The method according the  claim 18 , further comprising: functionalizing the one of more microfluidic chambers prior to loading the cells, to monitor cell substrate interactions or for the detection of biochemical targets excreted or extracted from the cells.